Long-term Results of Treatment of Patients with Non-proliferative Diabetic Retinopathy Angioprotectors

Purpose: Optimization of approaches to the treatment of early stages diabetic retinopathy based on modern diagnosis and monitoring of patients with type 2 diabetes.

Patients and methods: It was examined 90 patients (180 eyes) with type 2 diabetes with DR: women (74.4%) and men (25.6%), age 63,7±2,3 years. All groups matched by sex and age: Group 1 — control (healthy individuals without diabetes); Group 2 — Patients with DR0 (30 patients, 60 eyes) with type 2 diabetes without DR; 3 group — patients with DR I without DMO with type 2 diabetes (30 patients, 60 eyes). Patients 2 and 3 groups was treated with conservative treatment angioprotectors drug-Doxi-Hem® registered in Russia. The drug was administered in a dose of 500 mg three times a day for six months. Monitor patients for six months of receiving Doxi-Hem® preparation consisted of monthly conventional ophthalmic examination, including further analysis of BCVA (BCVA), light sensitivity of the macula (SM) as a result of fundusmikroperimetrii MAIA, central retinal thickness (PZT) based on the results of the optical coherence tomography (OCT). We take into account the compensation of diabetes on the level of glycated hemoglobin (HbA1C) blood.

Results: When monitoring patients with type 2 diabetes to optimize the treatment of established efficacy and safety of drug therapy Doxi-Hem® in the prevention and treatment of pre-clinical and early manifestations of DR (DR0, DR1), which is confirmed by reliable positive dynamics of visual functions (BCVA, p <0.05, before treatment 0,8±0,02, after treatment increased to 0,92±0,02), morphological reduction in retinal thickness (PZT, p <0.05; before treatment 272,3±5,8 mm, after treatment 241.5±15.8 um), increased sensitivity of the macula (CM, p <0.05, before treatment 22.2±1.5 dB, after treatment 27.0±3.2 dB). Required control the severity of type 2 diabetes on the target level of blood glycosylated hemoglobin (HbA1C).

Conclusion: Optimization approaches to HIV prevention, treatment of pre-clinical and early manifestations of DR (DR0, DR1) with the use of drug therapy angioprotector Doxi-Hem® based on modern diagnosis and monitoring of patients with type 2 diabetes for a long time will allow to stabilize and maintain clinical and morphological condition of the retina. Modern diagnostics, including the definition of the ophthalmological examination: visual acuity, central retinal thickness, macular light sensitivity as well as the definition and stabilization of important biochemical indicator of blood glycated hemoglobin (HbA1C) will not prevent the development of more severe stages of DR. In patients with type 2 diabetes without signs of diabetic retinopathy (DR0), while maintaining high visual acuity and normal retinal thickness showed a significant and meaningful reduction in the light sensitivity of the retina of the macula, which allows to start treatment with redox Doxi-Hem® at the preclinical stage (DR0).

1. International Diabetes Federation. IDF Diabetes Atlas, 6th ed. Brussels, Belgium: International Diabetes Federation, 2013.

2. ACCORD Study Group; ACCORD Eye Study Group, Chew EY, Ambrosius WT, Davis MD; Danis RP et al. Effects medical therapies retinopathy progression in type 2 diabetes. N.Engl. J. Med. 2010;363(3):233-44. DOI: 10.1056 / NEJMoa1001288.

3. Cheung NI, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010 Jul 10;376(9735):124-36. DOI: 10.1016 / S0140-6736 (09) 62124-3.

4. Ametov AS Lysenko MA [Type 2 diabetes and cardiovascular disease: a clash of two global epidemics of non-communicable]. Sakharnyy diabet 2 tipa i serdechnososudistye zabolevaniya: stolknovenie dvukh global’nykh neinfektsionnykh. [Russian Ophthalmological Journal]. Rossiyskiy oftal’mologicheskiy zhurnal. 2011;19(13):802-804. (in Russ).

5. Ryabina MV Sukhanova GA [A new approach to the treatment of recurrent hemorrhages into the vitreous of patients with diabetic retinopathy]. [Russian Ophthalmological Journal]. Rossiyskiy oftal’mologicheskiy zhurnal. 2012;5(3):43-47.

6. Kiseleva TN [Anthocyanosides role in the correction of microcirculatory hemodynamics and eyes when ophthalmopathology]. Rol’ antotsianozidov v korrektsii narusheniy mikrotsirkulyatsii i gemodinamiki glaza pri oftal’mopatologii. [Russian Ophthalmological Journal]. Rossiyskiy oftal’mologicheskiy zhurnal. 2013;6(1):108-112. (in Russ).

7. ACCORD Study Group; ACCORD Eye Study Group; Chew E.Y., Ambrosius W.T., Davis M.D .; Danis R. P. et al. Effects ofmedical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010 Jul 15;363(3):233-44.

8. Hodzhaev NS, Kuntysheva KE [Diabetic retinopathy and hypertension: clinical and pathophysiological aspects of comorbidity and rational drug correction]. Diabeticheskaya retinopatiya i gipertonicheskaya bolezn’: klinikopatofiziologicheskie aspekty komorbidnosti i ratsional’noy medikamentoznoy korrektsii. [Siberian Scientific Medical Journal]. Sibirskiy nauchnyy meditsinskiy zhurnal. 2014;34(3):72-75. (in Russ).

9. Khodzhaev NS Chernykh VV. Kuntysheva KE [Clinico-pathogenetic and prognostic significance of factors of progression of diabetic retinopathy in the background of essential hypertension after phacoemulsification]. Kliniko-patogeneticheskoe i prognosticheskoe znachenie faktorov progressirovaniya diabeticheskoy retinopatii na fone gipertonicheskoy bolezni posle fakoemul’sifikatsii. [Оphthalmology in Russia]. Oftalmologiya. 2016;13(1):25-32. (in Russ).

10. Garay RP, Hannaert P, Chiavaroli C. Calcium Dobesilate in the Treatment of Diabetic Retinopathy. Treatments in Endocrinology [Internet]. Springer Science + Business Media. 2005;4(4):221-32. DOI: 10.2165 / 00024677-200504040-00003

11. Ribeiro ML, Seres AI, Carneiro AM, Stur M, Zourdani A, Caillon P, et al. Effect of calcium dobesilate on progression of early diabetic retinopathy: a randomised double-blind study. Graefe’s Archive for Clinical and Experimental Ophthalmology [Internet]. Springer Science + Business Media. 2006 Jun9;244(12):1591-600. DOI: 10.1007 / s00417-006-0318-2

12. Padilla E, Ganado P, Sanz M, Zeini M, Ruiz E, Triviño A, et al. Calcium dobesilate attenuates vascular injury and the progression of diabetic retinopathy in streptozotocin-induced diabetic rats. Diabetes Metab Res Rev [Internet]. WileyBlackwell. 2004 May 28;21(2):132-42. DOI: 10.1002 / dmrr.487

13. Zhang X, Liu W, Wu S, Jin J, Li W, Wang N. Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis. Sci China Life Sci [Internet]. Springer Science + Business Media. 2014 Dec 20;58(1):101-7.

14. Suschek C, Kolb H, Kolb-Bachofen V. Dobesilate enhances endothelial nitric oxide synthase-activity in macro- and microvascular endothelial cells. British Journal of Pharmacology [Internet]. Wiley-Blackwell. 1997 Dec;122(7):1502-8. DOI: 10.1038 /sj.bjp.0701512

15. Javadzadeh, A .; Ghorbanihaghjo, A .; Adl et al. Calcium dobesilate reduces endothelin-1 and highsensitivity C-reactive protein serum levels in patientswith diabetic retinopathy. Mol Vis. 2013;19: 62-8. Epub 2013 Jan 10.

16. Angulo J, Peiró C, Romacho T, Fernández A, Cuevas B, González-Corrochano R, et al. Inhibition of vascular endothelial growth factor (VEGF) -induced endothelial proliferation, arterial relaxation, vascular permeability and angiogenesis by dobesilate. European Journal of Pharmacology [Internet]. Elsevier BV; 2011 Sep; 667(1-3):153-9. DOI: 10.1016 / j.ejphar.2011.06.015

17. Demirtas S. Can calcium dobesilate be used safely for peripheral microvasculopathies that require neoangiogenesis? Medical Science Monitor Basic Research [Internet]. International Scientific Literature. 2013;19:253-7. DOI: 10.12659 / msmbr.889427

18. Neroev VV, Zaitseva OV, Kiseleva TN [Features of ocular blood flow in patients with high-risk proliferative diabetic retinopathy]. Osobennosti glaznogo krovotoka u patsientov s oslozhnennoy proliferativnoy diabeticheskoy retinopatiey. [Medical imaging]. Meditsinskaya vizualizatsiya. 2016;1:18-24. (in Russ.)

19. Wong EN, Mackey DA, Morgan WH, Chen FK. Inter-device comparison of retinal sensitivity measurements: the CenterVue MAIA and the Nidek MP-1. Clinical & Experimental Ophthalmology [Internet]. Wiley-Blackwell. 2016 Jan;44(1):15–23. DOI:10.1111/ceo.12629

20. Midena E, Vujosevic S. Microperimetry in diabetic retinopathy. Saudi Journal of Ophthalmology [Internet]. Elsevier BV. 2011 Apr;25(2):131–5. DOI:10.1016/j.sjopt.2011.01.010

21. Cennamo G, Vecchio EC, Finelli M, Velotti N, de Crecchio G. Evaluation of ischemic diabetic maculopathy with Fourier-domain optical coherence tomography and microperimetry. Canadian Journal of Ophthalmology / Journal Canadien d’Ophtalmologie [Internet]. Elsevier BV. 2015 Feb;50(1):44–88. DOI:10.1016/j.jcjo.2014.08.005

22. Kim DY, Yang HS, Kook YJ, Lee JY. Association between Microperimetric Parameters and Optical Coherent Tomographic Findings in Various Macular Diseases. Korean J Ophthalmol [Internet]. Korean Ophthalmological Society (KAMJE). 2015;29(2):92. DOI:10.3341/kjo.2015.29.2.92

23. Raman R, Nittala M, Gella L, Pal S, Sharma T. Retinal sensitivity over hard exudates in diabetic retinopathy. Journal of Ophthalmic and Vision Research. [Internet]. Medknow. 2015;10(2):160. DOI:10.4103/2008-322x.163771

24. Khodzhaev N.S., Proshina E.Ya., Pozharnitskiy M.A. [Clinical experience with angioprotectors Doxey-chem in diabetic retinopathy]. Klinicheskiy opyt primeneniya angioprotektora Doksi-khem pri diabeticheskoy retinopatii. [Russian ophthalmological journal]. Rossiyskiy oftal’mologicheskiy zhurnal. 2003.4 (3):129–131. (in Russ).

25. Oganezova Zh.G., Egorov E.A. [Application angioprotectors in the treatment of diabetic angiopathy: focus on calcium dobesilate]. Primenenie angioprotektorov pri lechenii diabeticheskoy angiopatii: fokus na dobezilat kal’tsiya. [Russian ophthalmological journal]. Rossiyskiy oftal’mologicheskiy zhurnal. 2015;4:201–204. (in Russ).

26. Statsenko M.E., Sobolevskaya N.V. [The effectiveness of calcium dobesilate in the treatment of diabetic microangiopathy]. Effektivnost’ dobezilata kal’tsiya v kompleksnoy terapii diabeticheskikh mikroangiopatiy. Consilium medicum. 2012;14(1):70–75. (in Russ).

27. Ponomareva A.I., Kameneva E.S., Kompaniets O.G. [Calcium dobesilate pharmacotherapy microangiopathy]. Dobezilat kal’tsiya v farmakoterapii mikroangiopatiy. Consilium Medicum. 2012;10:126–127. (in Russ).

28. Shadrichev F.E., Grigor’eva N.N., Rakhmanov V.V. [New opportunities in preventing progression of diabetic retinopathy in patients with diabetes of type II]. Novye vozmozhnosti v profilaktike progressirovaniya diabeticheskoy retinopatii u bol’nykh sakharnym diabetom vtorogo tipa. [Endocrinology: news, opinions, and training]. Endokrinologiya: novosti, mneniya, obuchenie. 2014;3(8):51-57. (in Russ).

29. Bondar’ I.A., Shabel’nikova O.Yu. [Genetic basis of type 2 diabetes]. Geneticheskie osnovy sakharnogo diabeta 2 tipa. [Diabetes]. Sakharnyy diabet. 2013.(4):11–16. (in Russ).

30. Ametov A.S., Lysenko M.A. Sakharnyy diabet 2 tipa i serdechno-sosudistye zabolevaniya: stolknovenie dvukh global’nykh epidemiy neinfektsionnye. [Type 2 diabetes and cardiovascular disease: a clash of two global epidemics of noncommunicable]. [Russian ophthalmological journal]. Rossiyskiy oftal’mologicheskiy zhurnal. 2011;19(13):802-804. (in Russ).

31. Izmaylov A.S., Kotsur T.V. [The use of diode laser modes mikrofotokoagulyatsii and laser photocoagulation for the treatment of high density of diabetic macular edema]. Primenenie diodnogo lazera v rezhimakh mikrofotokoagulyatsii i lazernoy koagulyatsii vysokoy plotnosti dlya lecheniya diabeticheskogo makulyarnogo oteka. [Ophthalmology journal]. Oftal’mologicheskie vedomosti. 2016. 9(2):27-29. (in Russ).

32. Lipatov D.V., Kuz’min A.G., Tolkacheva A.A., Chistyakov T.A. [Features proliferative process in patients with diabetic retinopathy and its treatment]. Osobennosti proliferativnogo protsessa u patsientov s diabeticheskoy retinopatiey i ikh lechenie. [Russian Medical Journal. Clinical Ophthalmology]. Rossiyskiy meditsinskiy zhurnal. Klinicheskaya oftal’mologiya. 2016;17(2):107-111. (in Russ).